EXPERIMENTAL INFECTION OF COMMON MARMOSET WITH EASTERN EQUINE ENCEPHALITIS VIRUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 东方马脑炎病毒（Eastern Equine Encephalitis，EAE）是一种甲病毒，可引起人类、马和鸟类疾病。 该病毒在美国东部流行，由蚊子传播，导致人类大部分无症状感染。 那些出现症状的人会经历类似流感的症状，脑炎，昏迷和死亡。 那些发展成脊髓灰质炎的人的总死亡率是30%，而那些恢复的人有轻度到重度的神经损伤。 由于这种病毒有可能被用作生物武器，因此被指定为一种特定的病毒。 目前没有足够的非人灵长类动物模型可用于测试疫苗或治疗干预的疾病。 目前的研究旨在发展普通绒猴作为一种模型，为疟疾。 通过鼻内滴注用106 pfu的EEEV北美株（致病株）对总共三只动物进行实验性接种。 第二组3只动物通过相同途径接种106 pfu南美EEEV毒株（非致病性毒株）。 感染后每天观察动物长达15天。 在预定时间点采集血液用于血液学和生化分析，同时在每个血液采集时间点采集体温数据。 那些接种了北美菌株的动物经历了高温（104华氏度），并出现厌食症，抑郁症和神经系统疾病的症状。 动物在第5天严重濒死，并人道处死。 未从血液中回收病毒，仅在脑组织中检测到病毒。 H&E染色组织切片检查显示脑膜脑炎。 相比之下，接种南美EEEV的动物基础体温没有升高，也没有表现出疾病的临床体征。 在接种后24小时开始检测到一过性病毒血症，到第4天达到峰值103 pfu/ml。 感染后第7天，血液中未检测到病毒。 动物保持健康，直至15天项目结束。 初步研究的初步数据提供了证据，支持普通绒猴作为模型的实用性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eastern Equine Encephalitis (EEE) virus is an alphavirus that causes disease in humans, horses and birds. The virus in endemic in the Eastern United states and is transmitted by a mosquito resulting in mostly asymptomatic infections in humans. Those that develop symptoms experience flu-like symptoms to encephalitis, coma and death. The overall mortality for those that develop EEE is 30% while those that recover have mild to severe neurologic damage. Because of the potential to use this agent as a biological weapon, the virus is designated as a select agent. There are currently no adequate nonhuman primate models available to test vaccines or therapeutic interventions for the disease. The current study seeks to develop the common marmoset as a model for EEE. A total of three animals were experimentally inoculated with 106 pfu of a North American strain (pathogenic strain) of EEEV by intranasal instillation. A second group of three animals was inoculated with 106 pfu of a South American EEEV strain (nonpathogenic strain) by the same route. Animals were observed daily for up to 15 days post infection. Blood was collected at predetermined time points for hematology and biochemical analysis while temperature data was collected at every blood collection time point. Those animals that were inoculated with the North American strain experienced elevated temperature (104 degrees F) and developed anorexia, depression and neurological signs of disease. Animals become severely moribund by day 5 and were humanely euthanized. Virus was not recovered from blood and was only detected in brain tissue. Examination of H&E stained tissue sections revealed meningoencephalitis. In contrast, those animals inoculated with South American EEEV experienced no elevation in basal temperature and showed no clinical signs of illness. Transient viremia was detected beginning at 24 hours post inoculation peaking at 103 pfu/ml by day 4. No virus was detected in the blood after day 7 post infection. Animals remained healthy until project end of 15 days. The preliminary data from the pilot study provides evidence to support the utility of the common marmoset as a model for EEE.